We overview recent advances in the theoretical modeling, in particular via numerical simulation, of various vital human erythrocyte phenomena. The review is novel in how it interconnects a range of analysis within a coherent framework and focuses on extracting from them specific suggestions for experimental studies focused on, either validation of the analysis' mechanistic basis, or uncovering heretofore unrecognized effects and mechanistic understanding. In some cases, new analysis is described to fill in gaps and expand on previously published findings. Moreover, the presentation makes clear what new knowledge is required to further advance what is envisioned to be a truly quantitative approach to understanding the human blood cell. The entire treatment is based on, and designed to directly couple to, experimental observations. A specific goal is to point to a more quantitative and predictive approach to understanding human erythrocyte phenomena and their connectivity. Among the phenomena analyzed are: (1) membrane skeletal dynamics, per se, and how it is involved in (2) transmembrane molecular transport, e.g., glucose uptake; (3) red cell vesiculation, especially as it may occur during splenic flow; and (4) how skeletal dynamics affects both phenomena. Red cell flow is analyzed in complex flows such as oscillatory shear flow and during cell passage through splenic-like venous slits. We show, and perhaps remarkably, that the deformation modes that develop during both, apparently disparate, flows are actually quite similar. This finding suggests a novel methodology for experimentally studying splenic-like vesiculation. Additional analysis is presented that examines the effect of skeletal defects, including disruptions in its membrane connectivity, on molecular transport and vesiculation. As an example, we explore a reported effect of skeletal disruptions at the anion transporter, Band 3, on glucose uptake and efflux at the GLUT1 which are connected via the spectrin skeleton.

中文翻译：

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重要的红细胞现象：理论、建模和模拟能提供什么？

我们概述了各种重要人类红细胞现象的理论建模的最新进展，特别是通过数值模拟。该评论新颖之处在于它如何在一个连贯的框架内将一系列分析相互关联，并侧重于从中提取针对实验研究的具体建议，重点是验证分析的机械基础，或揭示迄今为止未被认识的影响和机械理解。在某些情况下，描述了新的分析来填补空白并扩展先前发表的发现。此外，该演示还明确了需要哪些新知识来进一步推进所设想的真正定量方法来理解人类血细胞。整个治疗基于并设计为直接与实验观察相结合。一个特定的目标是指出一种更定量和更具预测性的方法来理解人类红细胞现象及其连通性。分析的现象包括：(1) 膜骨架动力学本身，以及它如何参与 (2) 跨膜分子转运，例如葡萄糖摄取；(3) 红细胞小泡，特别是在脾血流时可能发生；(4) 骨骼动力学如何影响这两种现象。红细胞流在复杂流中进行分析，例如振荡剪切流和细胞通过脾样静脉裂隙的过程。我们表明，也许是值得注意的是，在这两种明显不同的流动过程中形成的变形模式实际上非常相似。这一发现提出了一种用于实验研究脾样囊泡的新方法。提供了额外的分析，检查骨骼缺陷的影响，包括其膜连接的中断，对分子运输和水泡形成的影响。例如，我们探讨了阴离子转运蛋白 Band 3 的骨骼破坏对通过血影蛋白骨架连接的 GLUT1 的葡萄糖摄取和流出的影响。